Chapter 400: Dynamic APT

Pang Xuelin smiled faintly, he was not as disappointed as Ashford, and the release of this test report made him determined to determine the next research direction.

Pang Xuelin said loudly: "Let me put aside my personal test report in advance, and then we will do a good job in two aspects." First, we have to figure out why the T virus in Alice's body is transformed into an ERV sequence, find out how this is biochemical, and I'll convince Alice to cooperate with your research. As for the other direction, it is the study of non-coding RNAs......"

"Non-coding RNA?"

Spruce and the others looked surprised.

Non-transcribed RNA involves the problem of how to control the T virus, and in the past six months, the laboratory has mainly studied how the T virus accelerates the metabolic rate of human cells and a series of biochemical reaction mechanisms, but has not done anything in how to inhibit the T virus.

Pang Xuelin didn't tell everyone about non-coding RNA.

Pang Xuelin smiled: "For the study of the T virus, in addition to figuring out how it invades the human body and a series of harms it produces, we also need to find ways to suppress this virus." Everyone should know about the gene silencing phenomenon caused by RNA interference, in a sense, the gene silencing phenomenon is likely to be a defense mechanism used to resist transposon or RNA viruses in the evolution of organisms, and it is an ancient antiviral strategy used by organisms. RNA interference is inextricably linked to non-coding RNA, so our main work in the future is to find out how the non-coding RNA interacts with each other and with proteins in the human body as much as possible. ”

Spruce and Berkeley glanced at each other, and Berkeley pondered for a moment before nodding, "That's a good idea." But there's a big problem. ”

"What's the problem?"

Pang Xuelin was a little curious.

"To study the interactions of non-coding RNAs with other non-coding RNAs and proteins within the cell, we have to have a very deep understanding of proteins," Berkeley said. In particular, the connection between the dynamics of proteins and their intrinsic functions must be done with the instruments in our current laboratories. ”

"In the case of proteins, although since the mid-twentieth century, when the crystal structure of hemoglobin was resolved, we have known a lot about the spatial structure of proteins and their complexes. Especially in recent years, with the development of structural analysis methodology, especially the rise of structural genomics, we can greatly accelerate the speed of analyzing the three-dimensional structure of proteins by means of crystal diffraction, nuclear magnetic resonance, cryo-electron microscopy, etc. ”

"But so far, we still can't infer the three-dimensional structure of a protein from its first-order sequence, let alone accurately predict its biological function, and it is difficult to accurately understand the function of a protein even under known three-dimensional conditions. The simple reason is that we lack an understanding of the temporal dimension of proteins. Protein is an entity with a certain spatial structure, and its three-dimensional properties, such as the well-known hydrophobic bags, set rings, etc., are closely related to its biological functions. ”

"However, in solution, proteins are in constant motion and change, and in living cells, proteins go through the process of folding, modifying, transporting, and assembling into complexes. The time scale of this movement varies with different proteins, the same protein in different environments, and different parts of the same protein. For example, in general, the active site of an enzyme is more motile and the secondary structure site is more rigid. Therefore, like the three-dimensional structure of proteins, the dynamic characteristics of proteins play an equally important role in determining protein function. ”

"Therefore, we must have the ability to observe the dynamics of proteins in real time at the atomic level, but due to the limitations of structural research methods, we can only capture a picture of proteins at a certain moment in time. However, in fact, proteins in solution do not have a static structure, as described in the crystal structure, but contain a dynamic process. From the perspective of physics, under the action of thermal motion, there is a huge conformational combination near the equilibrium structure of proteins, that is, conformational clusters. It is this conformational cluster that enables the diversity of protein-ligand binding strength and patterns. ”

"We still lack a clear understanding of how these conformational clusters recognize each other with other proteins, such as enzymes and substrates. In addition, after translation of proteins in eukaryotes, peptide chain folding, various modifications, transmembrane transport, ligand interaction and degradation processes, etc., how will these processes affect the dynamic conformation of proteins and thus regulate biological functions? Moreover, the time motion scale of protein is very wide, from the vibration of chemical bonds, the rotation of side chain groups, to the movement of the backbone, the peristalsis of the domain, and the flipping of the entire protein structure, etc., this process includes a very wide time scale from femtosecond to thousand seconds, so it is still difficult for us to observe the real-time motion of protein atoms at the level in the laboratory. ”

Pang Xuelin was curious: "Isn't it possible to use nuclear magnetic resonance technology?" I remember that the protein dynamics from picosecond to nanosecond can be observed through conventional relaxation experimental techniques, the movement of proteins from microseconds to milliseconds can be observed by means of CPMG relaxation discrete technology, paramagnetic relaxation enhancement and other technical means, and the movement of proteins from seconds to milliseconds can also be detected by combining hydrogen and deuterium exchange methods......"

Berkeley shook his head and said with a wry smile: "Professor Pang, you only know one thing, but you don't know the other, although we have now realized that the protein molecule completes the movement on the slow time scale through the fluctuations of the thermal equilibrium of some of its local atoms on the fast time scale, and even we can know the motion state of some atoms of the protein in some time scales, but this observation is still quite limited, and it is still a drop in the bucket for studying the dynamics of proteins as a whole." Today, we can only use molecular simulation techniques to study the precise motion of protein molecules from microseconds to nanoseconds, and even simulate the motion of longer time scales with some assumptions and simplifications. But this method only allows us to obtain the overall average characteristics of a certain number of proteins, and little is known about how individual protein molecules move......"

Pang Xuelin couldn't help frowning, he didn't expect that there would be such a problem.

But it shouldn't be, with the level shown by the umbrella company, since they can make something like T virus on the basis of the progenitor virus, it is impossible not to study the dynamics of individual protein molecules, how did they do it?

He looked away from Berkeley and confronted Ashford, who was sitting in the corner, never saying a word.

Ashford shook his head at Pang Xuelin, meaning that it was inconvenient to say it now.

Pang Xuelin said: "In that case, then let's put this aside for now, Dr. Ashford, you come with me, I have something to look for you." ”

Soon, everyone left the laboratory one after another, and Pang Xuelin also took Ashford to his office.

Pang Xuelin said: "Dr. Ashford, how did the umbrella company solve the problem that Professor Berkeley said just now?" ”

Ashford smiled wryly: "The various cutting-edge experimental instruments and equipment within the umbrella company are much higher than the outside world, and if we want to study non-coding RNA and its relationship with proteins at the atomic scale, I am afraid we will have to add a dynamic APT to the laboratory." ”

"Dynamic APT?"

Pang Xuelin looked at Ashford with some puzzlement.

Ashford's: "The so-called APT is the atomic probe chromatography technology in materials science, which can confirm the type of atom and intuitively reconstruct its spatial position, relatively realistically display the three-dimensional spatial distribution of atoms of different elements in the material, and become an analysis and testing method with the highest spatial resolution. Dynamic APT, on the other hand, is to observe the movement of protein molecules in real time through such a probe, which is a device that only umbrella companies have. ”

Pang Xuelin was slightly stunned, a little crying and laughing, he didn't expect that he wanted to study a way to kill the T virus, and the instruments and equipment still needed to get support from the umbrella company.

"But how do you get Spencer to willingly send me a dynamic APT?"

Pang Xuelin frowned and pondered.

At that moment, the electricity on the desk suddenly went off.

Pang Xuelin picked up the phone.

Claire's voice came from the other end of the phone: "Professor Pang, a man named Albert Wesker has come to the Umbrella Company, and he said he wants to see you." ”

Pang Xuelin was slightly stunned, and hurriedly got up and said, "Okay, I'll go back to the ground immediately." ”

"What's wrong?"

Ashford curious.

Pang Xuelin laughed and said, "Albert Wesker is here, maybe I will be able to solve the problem of dynamic APT soon." ”

……

Returning to the ground from the laboratory, Pang Xuelin went straight to the tarmac.

Today's Kempten base has changed a lot compared to half a year ago.

The construction of prefabricated houses and water and electricity grid heating in the base has been completed.

The power facilities mainly rely on a small mobile molten salt nuclear reactor provided by the umbrella company, which is equivalent to a small and power bank, which can fully meet the living needs of more than 10,000 people in the Kempten base.

The construction of the defensive wall around the base has also come to an end, the area surrounded by the defensive wall is about 2.5 square kilometers, the living area only occupies one-fifth of the total area of the base, and the rest of the area is basically dominated by farmland and pasture.

Public service units such as schools, police stations, and hospitals have also been reactivated.

In addition, there are public cafeterias and public bathhouses in the base.

According to Pang Xuelin's plan, after a year, the base will basically reach self-sufficiency, and it will be completely free from dependence on the umbrella company.

At this time, on the tarmac, Claire was arranging for people to unload the cargo from the helicopter.

A man who looked to be in his twenties, wearing sunglasses and meticulously combed hair, was waiting patiently.

Seeing Pang Xuelin coming over, the man turned his gaze to Pang Xuelin, with a sense of scrutiny in his eyes.

Pang Xuelin stretched out his hand and smiled: "Mr. Albert, I am Pang Xuelin." ”

"Hello Mr. Pang, I'm Albert Wesker, and I've been commissioned by Mr. Spencer to take a look at the Kempten base."

Albert shook hands with Pang Xuelin and said lightly.

"Sure enough, it's him!"

Pang Xuelin said secretly in his heart, but he remained silent on the surface, and said: "Mr. Albert, welcome to the Kempten base, I need to show you around the base first." ”

Spencer's three subordinates, Alex Wesker, Albert Wesker and William Birkin, William Birkin and Musk were mixed up, and Alex Wesker stayed by Spencer's side, in a sense, Albert Wesker can be regarded as the number two person in the Umbrella Company.

Albert said: "Professor Pang, there is no need to visit the base, I have already taken a general look on the plane just now, and today I came here on behalf of Mr. Spencer, mainly for two things." First, when you and Mr. Spencer were talking about working together, the condition was that we would develop a new generation of viruses based on the T virus, and I wanted to know how far we had progressed in the development of that virus. On the other hand, I came here this time to collect some blood and cell samples from you, and the samples I got from you last time have been used up. ”

Pang Xuelin was slightly stunned, with a helpless look on his face, and said: "There is no problem in collecting specimens, as for the research and development of new viruses, we have encountered some problems. ”

"What's the problem?"

Albert Road.

Pang Xuelin said: "Mr. Albert, presumably the R&D department of the umbrella company has already tested the ERV sequence on me, you should not have found the same sequence information with the T virus from it, right?" ”

Albert nodded.

He came here today mainly for this issue.

At the beginning, Pang Xuelin cooperated with Spencer, and Spencer hoped to get a new evolutionary direction from Pang Xuelin, and also took blood samples from Pang Xuelin.

As a result, after the scientists of the umbrella company conducted in-depth research on Pang Xuelin's genetic sequence, they were unable to find any homologous information related to the T virus from Pang Xuelin.

That's a bit of a hassle.

You must know that whether it is Spencer, Wesker, Muscu or even Alice, after they are infected with the T virus, the homologous sequence of the T virus is basically detected in the ERV in the body, and Spencer also hopes to find a similar sequence from Pang Xuelin, and then refer to Pang Xuelin's ERV sequence to find the improvement direction of the T virus.

Who would have thought that Pang Xuelin's ERV sequence was completely different from theirs.

That's more troublesome.

Because there are thousands of ERV sequences in the human body, no one knows which ones are useful and which ones are not.

It is basically impossible for the scientists of Umbrella to sift through the useful information from Pang Xuelin's ERV sequences without taking ten or eight years.

Spencer couldn't wait that long, since the scientists inside the umbrella company couldn't do it, he had to pin his hopes on Pang Xuelin, which was the main reason why he sent Albert Wesker to find Pang Xuelin.

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